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Vaginal pH, Estrogen and Genital Atrophy

Murray A. Freedman, MS, MD

Vaginal pH in women of reproductive age is typically 3.5-4.5; pH values in this range have been accepted for decades as representative of the normal vaginal ecosystem. Sufficient amounts of estrogen are required to maintain this acidic environment; specifically, adequate vaginal vascularization in the dermis and a glycogen-rich, stratified squamous epithelium, which acts in concert with lactobacilli to produce hydrogen peroxide and lactic acid.

In the estrogen-deficient postmenopausal woman, however, atrophy of the vaginal epithelium has been associated with vaginal dryness, and evidence is presented to suggest that vaginal pHrises to > 4.5 in 95%of women within 12 months of becoming hypoestrogenic. The homologues of the urogenital sinus in the embryo (the urethra, trigone and distal vagina) are extremely sensitive to estrogen deficiency, and contraction of the introitus becomes problematic. While lubricants may diminish dryness, it is the involutional contraction of the introitus that predisposes women to progressively worsening dyspareunia and sexual dysfunction.

Of clinical importance is the fact that these untoward atrophic changes in urogenital tissues are preventable with the use of very small amounts of topical estrogen. FDA approval criteria for drugs with efficacy in preventing/treating genital atrophy include the restoration or “normalization” of vaginal pHand the Vaginal Maturation Index (VMI), both of which are considered surrogate markers for vaginal health. Other parameters of vaginal health and atrophic change were included in a “vaginal health index,” as proposed by Bachmann1 (including overall elasticity, fluid secretion, epithelial mucosa, and moisture), but measurement of vaginal pH alone is an easy, inexpensive, quantifiable, reproducible evaluation that correlates well with other laboratory evaluations of vaginal epithelium, such as the VMI.2

Figure 1. Photomicrograph depicting normal (A) and atrophic (B) vaginal epithelium. Note the absence of glands in A and B, and the paucity of blood vessels in the dermis in B.

Abundant vasculature in the dermis and a stratified, glycogen-rich epithelium are also prerequisites for sufficient lubrication during the arousal phase of the female sexual response cycle (Figure 1). Because there are no glands in the vagina, per se, adequate lubrication in females is dependent upon a transudation of fluid across the epithelium, and dryness is a frequent complaint in women with genital atrophy due to insufficient estrogen. This atrophic change is frequently associated with dyspareunia, and the use of lubricants is often beneficial in such patients. But the discomfort these women experience involves far more than just vaginal dryness.While the primary purpose of this article is to explore the prevalence of genital atrophy in postmenopausal women asmeasured by a surrogate marker (vaginal pH), the impact of the involutional change at the introitus — and, consequently, upon sexuality—warrants discussion.

Genital Atrophy and Sexuality

Of the three major factors that can adversely affect sexuality in the postmenopausal woman (age, partnership issues, and ovarian and adrenal hormone deficiency),3-5 hormone deficiency (specifically estrogen) is the subject of this review. The estrogen/ genital atrophy connection is well recognized, but its prevalence is vastly underestimated. It has been reported that vasomotor symptomsmay affect up to 85% of estrogen-deficient women,6 and the National Osteoporosis Foundation estimates that 55% of untreated women over the age of 50 will develop osteoporosis. 7 There are no data, however, that accurately assess the prevalence, progression or severity of genital atrophy.

Prevalence of Genital Atrophy after Discontinuation of ET

To assess how rapidly the effects of hypoestrogenism were detectable in the vagina, the author studied 400 postmenopausal women who discontinued estrogen therapy (ET) after publication of the findings from theWomen’sHealth Initiative in July 2002.8 Monitoring was accomplished with a measurement of vaginal pH obtained at the patient’s routine office visit, followed by subsequent measurement after the patient had been off ET for at least 3 months but for less than 12 months. Of the 400 women, 381 (95%) had pH values > 4.5 within 12 months of discontinuing ET (Table). Ten of the 19 who maintained “normal” pH values were obese (body mass index > 30) and were producing significant amounts of endogenous estrogen (serum estradiol values > 20 pg/mL). Accordingly, the data suggest that the prevalence of demonstrable change in vaginal pH in women who are truly hypoestrogenic approaches 98%, and this change occurs within 12 months of discontinuing ET.

Figure 2. Embryologic development of the genital tract at 4-6 weeks. The trigone, urethra, vulva and distal vagina (insert) are homologues of the urogenital sinus.

Introital Stenosis

Themost impressive clinical finding among the 400 patients studied was the rapid contraction and loss of elasticity at the introitus. In retrospect, this should not have been unexpected because it is consistent with the embryologic development of the genital tract, as represented in Figure 2. The urogenital sinus in the embryo is the anlage of the trigone, urethra, and distal vagina and vulva; these are the structures (which are of endodermal origin) that have the highest concentration of estrogen receptors in the female body.9,10 The upper vagina and other Mullerian elements (ie, the uterus) are of mesodermal origin and, as such, they are not as exquisitely sensitive to estrogen. In markedly hypoestrogenic women (serum estradiol <10 pg/mL) the vulva and vagina can be shown to exhibit early involutional change within 12-24 months. Figure 3 demonstrates the morphologic change seen in the fourchette of a 55-year-old woman who had three vaginal deliveries but who discontinued ET 2 years previously. This degree of introital stenosis is also seen in much younger women who experience premature menopause; in the presence of significant estrogen deficiency (<20 pg/mL), the involutional change is progressive over time, irrespective of age.

Figure 3. Contraction of the introitus in a 55-year-old woman (P 3003; 3 vaginal deliveries) who stopped hormone therapy 2 years previously. Note the early involutional vulvar and vaginal change in conjunction with marked hypoestrogenism.

Contraction of the introitus in estrogen-deficient women typically occurs so insidiously that it often goes unnoticed at the annual visit. There is also concomitant but subtle loss of elasticity in the vulvovaginal tissue around the introitus. Among the 400 patients who are still being followed in the previously described study, the upper two-thirds of the vagina is far less affected by atrophy as compared with the compromise occurring at the fourchette. The vestibule actually loses much of its concavity and, as the introitus contracts, it becomes somewhat of a narrowed, fibrotic channel or tunnel. This early atrophic change at the introitus, rather than the vagina itself, is clinically quite important as it pertains to dyspareunia. Clinically, this contraction at the introitus can be confused with vaginismus, but it is actually anatomically distal to the levator muscles. This predilection for contraction and loss of elasticity of the components of the superficial urogenital triangle and carunculae hymenales is depicted in Figure 4.

Figure 4. Shaded areas (green) represent involution of the medial portions of the superficial urogenital triangle (which includes the vestibular bulb as well as the bulbocavernosus and superficial transverse perineal muscles).

Sexual Function in the Postmenopausal Woman

While the insipient change in vulvovaginal morphology associated with estrogen deficiency often goes undetected during the routine examination, pain with intromission becomes a frequent complaint among such patients. Leiblum and colleagues observed and reported that both sexual activity and estrogen are critical factors in preserving the functional integrity of the vagina in postmenopausal women.11 Dyspareunia obviously predisposes these women to developing sexual dysfunction. Because the early atrophy is so demonstrable at the introitus, parity also affects the degree of compromise of the fourchette. Figure 5 shows two similar patients who had been on ET since menopause. Patient A, who discontinued ET 3 years previously and discontinued sexual activity secondary to dyspareunia, demonstrates considerable contraction of elasticity of the entire introitus. Patient B, who has remained on ET, has no dyspareunia. Figure 6 depicts a patient who had 6 vaginal deliveries and a previously spacious, parous introitus. After being off ET for 4 years and after cessation of coital activity for 3 years secondary to dyspareunia, there is considerable contraction of the introitus, lichenification of the skin and loss of elasticity.

Once this degree of lichenification and “fibrotic” change occurs, the loss of elasticity and contraction of the introitus leads to dyspareunia; disuse atrophy then tends to compound the problemand the atrophic changes may become irreversible. Figure 7 contrasts a 79-year-old woman with a 53-year-old woman. The 53-year-old P 2002 woman (7A) discontinued ET 5 years previously because of “breast dysplasia” and suffers from marked dyspareunia while continuing to attempt sexual activity with the use of lubricants. The older P 3003 woman depicted in 7B has been widowed and celibate for more than 10 years, but has continued ET and demonstrates only minimal introital compromise.

Figure 7. Patient A is 53 years old and stopped estrogen therapy 3 years previously (breast dysplasia). Patient B is a 79-year-old who remains on estrogen therapy.

This illustrates once again that the amount and degree of atrophy is far more a question of estrogen deficiency than age. Additionally, coital activity contributes significantly to the anatomic integrity of the vagina and, in the absence of both estrogen and sexual activity, compromise of the fourchette develops rather rapidly.

Elevated vaginal pH is the result of an early epithelial change that is easily demonstrable, whereas the involutional change in the collagen, vasculature and functionality is much more subtle and progressively worsens over time. Lubricants may facilitate coital activity early on but, over time, the loss of elasticity and contraction leads to significant morphologic change and significant sexual dysfunction.

Figure 8. Artist’s representation of the progression of atrophic change (introital stenosis) that can be anticipated in most untreated postmenopausal women.

Summary and Conclusions

More than 95% of postmenopausal women can be expected to show a change in vaginal pH within 12-24 months of discontinuing ET, and most will demonstrate signs of genital atrophy on pelvic examination.8 The findings from the investigation described in this article suggest that the prevalence may actually approach 98% in women who are truly hypoestrogenic. It also suggests that introital stenosis and loss of elasticity are affected more by estrogen deficiency than by age, and Figure 8 illustrates the progression of atrophic change that can be anticipated in most untreated postmenopausal women.

There is considerable evidence that ET, especially if combined with sexual activity, mitigates atrophic changes. Because of the exquisite sensitivity of the distal vagina, urethra and trigone to estrogen, the atrophic genitourinary changes can actually be prevented/treated by the use of gentle vaginal dilatation and very small doses of topical ET applied as infrequently as twice-weekly (personal anecdotal experience as well as participation in several current clinical trials). The clinical implications of these involutional genitourinary changes, particularly as they pertain to sexual function, are beginning to be appreciated by many practitioners and their patients. Genital atrophy is clearly a frequent consequence of estrogen deficiency, and it is a quality-of-life issue that deserves far more attention than it currently receives.12 In view of the exquisite sensitivity of the urogenital tissues to estrogen, the prevention of female genital atrophy with the use of very small amounts of topical estrogen should be considered an important part of preventive health.

Murray A. Freedman, MS, MD, is Clinical Professor, Department of OB/GYN, The Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, GA

Dr. Freedman reports no potential conflicts related to the content of this article.